The prevalence of type 2 diabetes in Mexican Americans, a large minority ground in the United States, is two to three times higher than in Caucasians. The prevalence of end-stage renal disease (ESRD) in Mexican Americans with type 2 diabetes is almost 3-4 times higher than in Caucasians. The pathogenesis of diabetic nephropathy (DN) is not well understood but circumstantial evidence indicates the existence of a genetic basis for this disease. This grant application is a response to the RFA "Diabetic and Non- Diabetic Nephropathy Susceptibility Genes" (DK-99-005), and proposes to establish a Participating Investigation Center (PIC) at the University of Texas Health Science Center at San Antonio. As a family ascertainment center, the San Antonio PIC has the goal to ascertain approximately extended, multiplex families through ESRD patients recruited at dialysis and transplant clinics in San Antonio and South West Texas. In addition, this center will develop a quality control procedure for the family ascertainment. Questionnaires developed for this procedure will be available to all PICs. San Antonio is an 3excellent location to recruit and enroll Mexican American participants for genetic studies. Approximately 60% of inhabitants in San Antonio and South West Texas are Mexican Americans. More than half of the 5,700 ESRD patients in San Antonio and South West Texas are expected to be Mexican Americans. Therefore, the study population will be large enough to recruit the proposed set of 150 families. The San Antonio PIC proposes to perform three local research projects. (1) Phenotyping the set of families investigated in The San Antonio Family Diabetes Study (SAFADS, PI: Dr. M. Stern) for DN us under way. These families have already been genotyped with over 400 markers. We plan to have performed a variance component analysis (VCA) for the SAFADS families to identify possible candidate regions for DN genes by the end of the first year of funding. (2) Based on these early linkage results, a candidate region/gene analysis will be performed with the newly identified "ESRD pedigrees" applying VCA. (3) We will conduct a medical anthropological study to investigate how ESRD patients and their "healthy" relatives experience type 2 diabetes and DN when these diseases cluster in families.